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ISIS’ Final Reply to ACRE: Let the People
Decide
The evidence is laid bare, let the people judge for
themselves, say Dr. Mae-Wan Ho and
Prof. Joe Cummins.
Science advisors are anti-precautionary
In a long-running battle with UK’s scientific advisory committees
on GM, we at ISIS have repeatedly challenged their persistent refusal, either
to acknowledge scientific evidence suggesting genetic modification is not safe,
or to address areas of uncertainty with appropriate independent scientific
investigations.
The Advisory Committee on Releases to the Environment (ACRE) has
published its latest denial on its website last week [1]. The "ISIS’
Comments" referred to were made months earlier and posted on the GM Science
Review website. We have since submitted another critique [2], directed at the
GM Science Review First Report [3], a document remarkably similar in substance
to ACRE’s present (and past) responses: the same bland reassurances by
assertion, the same selective and misleading interpretation of the scientific
evidence.
The most striking aspect of the ACRE reply to ISIS is ACRE’s
underlying assumption that nothing about T25 (Chardon LL) maize should be
considered unsafe unless proven so, by a standard set to be as permissive as
possible for GM crops. The burden of proof is blatantly anti-precautionary.
It would be tedious to address ACRE’s latest response in detail,
which has, in any case, been overtaken by our critique [2] of the GM Science
Review Report.
Rather, we want to summarize, for the benefit of the public, the major
areas of disagreement between scientists like ourselves and those who advise
our government. Details are contained in the just published Independent Science
Panel (ISP) Report, The Case for a GM-Free Sustainable World [4]. Yet further
details are contained in Living with the Fluid Genome [5].
Some main points of contention that remain unanswered
There are both a priori and empirical evidence suggesting that GM is
inherently unsafe and unpredictable, which remain to be refuted.
1. GM is distinct from conventional breeding methods, including
mutations induced by X-rays or chemicals. It is unreliable, uncontrollable,
unpredictable and unstable; and introduces new risks (see below).
Ironically, the paper [6] cited by ACRE in support of transgenic stability
is actually one reviewed and exposed by ISIS two years ago, which showed
overwhelming instability, even on the most generous interpretation of a poor
dataset [7]. That paper is one example among many of the way scientific
evidence is misinterpreted and misreported by GM proponents: the claim of
transgenic stability made in the abstract is contrary to the evidence
reported in the rest of the paper.
Transgenic instability obviously compromises agronomic performance of
the GM crop, it is also an important safety issue. Apart from uncontrollable
and unexpected changes in the safety profile of the GM crop, there is the
possibility of transgenic DNA spreading directly to other organisms in a
process called horizontal gene transfer.
More seriously, ACRE appears to hold that ‘event specific’
molecular characterisation of transgenic lines is not necessary as evidence of
stability. (This is to ascertain that the transgenic DNA integrated into the
genome stays in the same form and in the same location in the plant’s
genome.) It states (p.7): "ACRE maintain that monitoring for stable expression
of transgenes rather than any inherent instability (which can occur in natural
DNA also) is sufficient and suitable. Event specific characterisation of
successive generations would offer no further information regarding the safety
of T25…" ACRE should be reminded that such characterisation is indeed
required by the European Directive for Deliberate Release.
2. GM DNA is definitely not the same as non-GM or natural DNA.
ACRE still maintains that transgenic DNA is no different from other
DNA. This is at best an untested, unjustified hypothesis. GM greatly increases
the scope of horizontal gene transfer and recombination, which pose the most
insidious dangers. The genetic material of any and every species on earth can
be recombined and transferred in the laboratory. There is no evolutionary
precedent for this situation. New genes and new combinations are being
introduced into our environment and food chain that have never existed.
The hypothesis of the equivalence of GM and non GM DNA has been
contradicted, prima facie, by the one single experiment ever done in
the world to test it [8]. One main difference may indeed be that GM DNA is
known to be structurally unstable from the beginning of genetic engineering,
and is hence more likely to spread than non GM DNA, possibly by horizontal gene
transfer.
3. Many GM DNAs possess ‘recombination hotspots’ making
them extra-unstable, and hence extra-prone to horizontal gene transfer and
recombination, with all the attendant risks.
The CaMV 35S promoter is
just one example of GM DNA with a recombination hotspot. We need not repeat our
concerns as these are widely known, and people will draw their own conclusion.
ACRE still does not mention that the promoter is active in animal and human
cells. ACRE claims our 1999 paper [9] was not subject to peer review, citing a
commentary in Nature Biotechnology, which was so obviously defamatory
and possibly libellous that the journal had to give us a right to reply.
4. Direct evidence of hazards inherent to the technology is swept
aside and misrepresented.
Topping the list of the direct evidence of
hazard inherent to the technology is the study of Pusztai and co-workers [10,
11], who found dramatic ‘growth-factor like’ effects in the stomach
and intestine lining of young rats fed GM potato for just 10 days, which were
not present either in rats fed non-GM potatoes or in rats fed non-GM potatoes
spiked with the transgene product. These results have been dismissed in the
absence of any attempt made to repeat the experiments.
5. Positive evidence of horizontal gene transfer denied and dismissed
as "very low frequency".
It is remarkable that there has been only one
single field monitoring experiment after millions of hectares of GM crops have
been planted, and just one human feeding trial involving 19 individuals fed a
single meal containing GM soya flour. Despite that, positive evidence of
horizontal transfer of GM DNA to bacteria in the soil and in the human gut has
been found. More remarkable still, our Government’s science advisors
persist in denying and dismissing this evidence.
ACRE says whether the transgene persists, after horizontal gene transfer
depends on ‘selection pressure’. We have exposed this to be false
[12]. Experiments dating back to the early 1990s have already found that
antibiotic resistance genes persist in bacteria that have acquired them long,
long after the antibiotic was withdrawn [13,14].
ACRE has further misrepresented Ho’s citation of Hohlweg &
Doerfler [15]. Ho said it was the latest of a series of papers [e.g., 16, 17]
dating back to the early 1990s which have shown that transgenic DNA can pass
through the gut and the placenta into the blood stream and end up in cells,
including those of the fetus and newborn. Hohlweg & Doerfler [15] did not
show transgenic DNA transfer to germline, but there was copious transfer to
somatic cells. Foreign DNA inserting into genomes of cells can lead to
"insertion mutagenesis" and "insertion carcinogenesis". Ho’s citation of
cancer arising from gene therapy experiments here is surely not "out of
context".
ACRE, in dismissing concerns about GM DNA transferring to gut bacteria,
state, "Microbes in samples from ileal digesta were cultured and despite
exhaustive attempts, no bacteria harbouring the transgene were isolated". This
is a misrepresentation, as the researchers, while reporting that they were
unable to isolate these particular bacteria, confirmed that there were bacteria
with the GM DNA present in the gut. Also, ACRE states, "In people with intact
tracts, they found that although transgene DNA from GM soya survived passage
through the human small bowel, it was completely degraded in the colon and was
not detected in faeces". But the researchers did not investigate if the GM DNA
had entered the bloodstream and cells of various tissues and organs, and we
know that this can happen [16, 17].
ACRE dismisses the possibility, suggested by the UK government’s
own commissioned research that Agrobacterium in the vector system used
in making transgenic plants, and found to remain in transgenic plants, may be a
vehicle for gene escape by horizontal gene transfer. ACRE makes the misleading
comparison between natural Agrobacterium found in the soil, which have
no ready access to mammalian cells, and the Agrobacterium in the transgenic
plants, which might easily be eaten by animals and human beings. Equating
genetically manipulated with natural Agrobacterium is also spurious, and
once again, depends on the unfounded, unjustified assumption that GM DNA is the
same as non-GM DNA.
ACRE says there is no evidence transgenic DNA can transfer to bacteria.
Here are two of the relevant publications cited, albeit incompletely, by the GM
Science Review First Report. Duggens and coworkers [18] found that the entire
coding sequence of the Cry1A(b) transgene could still be detected in
sheep rumen fluid 5 hours after feeding GM maize grains, and fragments more
than 200bp long were detected 24 hours later. Plasmid containing the transgene
and kanamycin resistance marker gene could still transfer the entire transgene
as well as kanamycin resistance to E. coli after being kept for 5
minutes in the sheep’s mouth. The authors remarked, "DNA released from
feed material within the mouth has potential to transform naturally competent
oral bacteria." Similarly, Mercer and coworkers [19] showed that both plasmid
and chromosomal DNA fragments were incompletely degraded after incubation in
the human mouth, and can still transform Streptococcus gordonii, which
normally lives in the mouth.
A host of other problems also dismissed by ACRE
Other
problems and hazards to health and the environment in growing GM crops, such as
toxicity and allergenicity of the transgene products, toxicity of herbicides
used with herbicide tolerant GM crops, herbicide tolerant weeds and transgene
contamination of non-GM and organic crops, are dealt with in the ISP Report
[4]. Needless to say, those are also ignored by ACRE.
Some definitive experiments that remain to be done
Like ACRE,
we see no point in going over the same disagreements or recycling the same
arguments. At a public meeting last November, Ho has submitted to the Advisory
Committee for Novel Foods and Processes (ACNFP) – ACRE’s sister
committee – a list of experiments that should be done to address areas of
uncertainty, and these are reproduced below, in a slightly improved form [4],
in the (vain) hope that ACRE will advise our government to commission such
research, and thereafter, to convey the results without distortion and
misrepresentation.
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Some definitive experiments that could inform on the safety
of GM food and crops
1. Feeding experiments similar to those carried out by
Pusztai’s team, using well-characterized transgenic soya and/or maize meal
feed, with appropriate, unbiased monitoring for transgenic DNA in the faeces,
blood and blood cells, and post-mortem histological examinations that include
tracking transfer of transgenic DNA into the genome of cells. As an added
control, non-transgenic DNA from the same GM feed sample should also be
monitored. In addition, the possible role of the CaMV 35 S promoter in
producing the ‘growth-factor-like’ effects in young rats should be
investigated.
2. Feeding trials on human volunteers using well-characterized
transgenic soya and/or maize meal feed, with appropriate, unbiased monitoring
for transgenic DNA and horizontal gene transfer in the mouth and in the faeces,
blood and blood cells. As an added control, non-transgenic DNA from the same GM
feed sample should also be monitored.
3. Investigation on the stability of transgenic plants in
successive generations of growth, especially those containing the CaMV 35S
promoter, using appropriate quantitative molecular techniques.
4. Full event specific molecular characterisation of all
transgenic lines to establish uniformity and genetic stability of the
transgenic DNA insert(s), and comparison with the original data supplied by the
biotech company to gain approval for field trials or for commercial
release.
5. Tests on all transgenic plants created by the
Agrobacterium T-DNA vector system for the persistence of the bacteria
and the vectors. The soil in which the transgenic plants have been grown should
be monitored for gene escape to soil bacteria. The potential for horizontal
gene transfer to the next crop via the germinating seed and root system should
be carefully monitored. |
Sources
1. "Response to ISIS Comments on ACRE’s Advice Concerning T25
Maize".
http://www.defra.gov.uk/environment/acre/advice/pdf/acre_advice34.pdf
2. See "GM Science Review Deeply Flawed", Science in Society 2003, 19,
www.i-sis.org.uk
3. GM Science Review First Report, July 2003 <www.gmsciencedebate.org.uk/report/default.htm>
4. Ho MW, Lim LC, et al. The Case for a GM-Free Sustainable World,
Independent Science Panel Report, ISIS and TWN, London & Penang, 2003.
5. Ho MW. Living with the Fluid Genome, ISIS and TWN, London &
Penang, 2003.
6. Gahakwa D, Maqbool SB, Fu X, Sudhakar D, Christou P and Kohli A.
Transgenic rice as a system to study the stability of transgene expression:
multiple heterologous transgenes show similar behaviour in diverse genetic
backgrounds. Theor Appl Genet 2000: 101: 388-99.
7. Ho MW. Questionable stability at JIC, ISIS News 9/10, July 2001,
ISSN: 1474-1547 (print), ISSN: 1474-1814 (online)
www.i-sis.org.uk reviewing ref. 6.
8. Bergelson J, Purrington CB, Wichmann G. Promiscuity in transgenic
plants. Nature 1998, 395, 25.
9. Ho MW, Ryan A and Cummins J. Cauliflower mosaic viral promoter –
a recipe for Disaster? Microbial Ecology in Health and Disease 1999 11,
194-7.
10. Ewen S and Pusztai A. Effect of diets containing genetically
modified potatoes expressing Galanthus nivalis lectin on rat small intestine.
The Lancet 1999, 354, 1353-4; also
http://plab.ku.dk/tcbh/PusztaiPusztai.htm
for Pusztai’s full rebuttal to his critics.
11. Pusztai A, Bardocz S and Ewen SWB. Genetically modified foods:
Potential human health effects. In Food Safety: Contaminants and Toxins,
(J P F D’Mello ed.), Scottish Agricultural College, Edinburgh, CAB
International, 2003.
12. Ho MW. Genetic Engineering Dream or Nightmare? TWN, Gateway,
Gill & Macmillan, Continuum, Penang, Bath, Dublin, New York, 1998, 1999,
Chapter on The Immortal Microbe and the Promiscuous Genes.
13. Tschape H. The spread of plasmids as a function of bacterial
adaptability. FEMS Microbiology Ecology 1992, 15, 23-32.
14. Schrag SJ & Perrot V. Reducing antibiotic resistance.
Nature 1996, 381, 120-1.
15. Hohlweg U. and Döerfler W. On the fate of plant or other
foreign genes upon the uptake in food or after intramuscular injection in mice.
Mol Genet Genomics 2001, 265, 225-33.
16. Schubbert R, Rentz D, Schmitz B and Döerfler W. Foreign (M13)
DNA ingested by mice reaches peripheral leukocytes, spleen and liver via the
intestinal wall mucosa and can be covalently linked to mouse DNA. Proc. Nat.
Acad. Sci. USA 1997, 94, 961-6.
17. Döerfler W, and Schubbert R. Uptake of foreign DNA from the
environment: the gastrointestinal tract and the placenta as portalsof entry.
Wien Klin. Wochenschr. 1998, 110, 40-4.
18. Duggan PS, Chambers POA, Heritage J & Forbes JM. Fate of
genetically modified maize DNA in the oral cavity and rumen of sheep.
British J. Nutrition 2003, 89, 159-66.
19. Mercer DK, Scott KP, Melville CM, Glover LA & Flint HJ.
Transformation of an oral bacterium via chromosomal integration of free DNA in
the presence of human saliva. FEMS Microbiology Letters 2001, 200,
163-7.
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